Tetradecyl lactate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Original tests performed according to an international guideline under GLP.

Justification for type of information:

Data originate from testing with shorter chain alkyl lactates.See section 13 for justification of read across.

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

ethyl lactate, n-butyl lactate, isobutyl lactate, and 2-ethylhexyl lactate

IUPAC Name:

ethyl lactate, n-butyl lactate, isobutyl lactate, and 2-ethylhexyl lactate

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Details on inhalation exposure:

Ethyl, n-butyl, and isobutyl-L-lactates were vapor studies, whereas 2-ethylhexyl-L-lactate was evaluated in an aerosol study and in a supplemental study comparing vapor and aerosol exposure.

Duration of treatment / exposure:

6 h

Frequency of treatment:

5 days a week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
ethyl-L-lactate: 0, 150, 600, or 2500 mg/m3 and 0, 25, 75, or 200 mg/m3
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
isobutyl-L-lactate: 0, 100, 200, 400, or 800 mg/m3
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
n- butyl- L-lactate: 0, 75, 200, or 600 mg/m3
Basis:
nominal conc.

Doses / concentrations 4

Remarks:

Doses / Concentrations:
2-ethylhexyl-L-lactate: 0, 75, 200, 600, or 1800 mg/m3
Basis:
nominal conc.

No. of animals per sex per dose:

ethyl, isobutyl, and the primary 2-ethylhexyl studies: 5 males and 5 females;
n-butyl and the supplemental 2-ethylhexyl study: 6 males

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not specified

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Main histopathological changes were observed in the nasal cavity (epithelial degeneration, hyperplasia, metaplasia, and inflammatory changes) larynx and trachea (slight epithelial hyperplasia and squamous metaplasia), and lungs (septal fibrosis).

Details on results:

2-Ethylhexyl-L-lactate appeared to be the most reactive in causing irritation of the nasal airways. In general, the local toxicity NOECs of alkyl lactate are lower than the systemic NOECs. This is probably mainly related to the activity of free lactic acid generated by enzymatic hydrolysis of the alkyl lactates.

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

200 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

ethyl, n-butyl, and isobutyl lactates

Sex:

male/female

Basis for effect level:

other: Local effects: hyperplasia of the nasal respiratory epithelium, including hyperplasia of goblet cells.

2

Key result

Dose descriptor:

NOAEC

Effect level:

600 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

butyl- L-lactate

Sex:

male

Basis for effect level:

other: Systemic toxicity

3

Key result

Dose descriptor:

NOAEC

Effect level:

200 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

butyl- L-lactate

Sex:

male

Basis for effect level:

other: Local effects

4

Dose descriptor:

NOAEC

Effect level:

800 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

isobutyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Systemic toxicity

5

Dose descriptor:

NOAEC

Effect level:

200 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

isobutyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Local effects

6

Dose descriptor:

NOAEC

Effect level:

600 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

2-ethylhexyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Systemic toxicity

7

Dose descriptor:

NOAEC

Based on:

test mat.

Remarks:

2-ethylhexyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Local effects (nasal epithelium)

Remarks on result:

not determinable

Remarks:

no NOAEL identified

8

Dose descriptor:

LOAEC

Effect level:

75 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

2-ethylhexyl-L-lactate (aerosol or vapor)

Sex:

male/female

Basis for effect level:

other: Local effects: slight focal hyperplasia of the nasal respiratory epithelium, including hyperplasia of goblet cells.

Target system / organ toxicity

Critical effects observed:

not specified